Case reports

Complete androgen insensitivity

syndrome
DOI: 10.5377/alerta.v5i2.14397

Rafael Alexis Contreras Cruz1*, Luis Ernesto Cortez Salvador2, Luis Villalta Morales3, Eduardo José Fuentes4 

1-2. Urology Department, Rosales National Hospital, San Salvador, El Salvador.

3. General Surgery Department, Rosales National Hospital, San Salvador, El Salvador.
4. Radiology Department, Rosales National Hospital, San Salvador, El Salvador.

Correspondence
calexis088@gmail.com

1. 0000-0003-3222-5119
2. 0000-0002-5327-166X
3. 0000-0003-3497-3444
4. 0000-0001-8424-3664

OPEN ACCESS Abstract

Presentation of the case. Phenotypically female patient, 18 years old, 46 XY karyotype, who was evaluated in a tertiary care
Síndrome de insensibilidad center for pediatric medicine due to primary amenorrhea. Physical evaluation found adequate breast development, female
completa a andrógenos external genitalia with slight hypoatrophy of the labia majora and minora, vaginal canal of 11 cm, ultrasound reports a linear
rudimentary uterus and images suggestive of ovaries, magnetic resonance describes the presence of a bilobed tubular
Suggested citation: structure composed of two nodular images, which are located adjacent to the bladder wall in their aspect posterior, lateral and
Contreras Cruz RA, Cortez superior right 27,4 × 15,4× 11,0 mm, left inguinal canal two images, one solid nodular, ovoid, isointense 37 × 21 × 13,8 mm
Salvador LE, Villalta (nodular), cystic 22,7 × 14,0 mm, congenital absence of uterus. Treatment. In the laparoscopic examination, the presence
Morales L, Fuentes EJ.
of gonads in the inguinal and para-bladder canals was detected, and both gonads were resected. Outcome. She was
Complete androgen
managed with analgesia, antibiotics and was discharged three days after surgery. The biopsy reported cryptorchidism of
insensitivity syndrome.
Alerta. 2022;5(2):112 -117. the right and left testis.
DOI: 10.5377/alerta.v5i2.14397
Keywords
Received: Androgen-insensitivity syndrome, testicular feminization, 46  XY gonadal dysgenesis, androgen effect, disorder of sex
May 13, 2022. differentiation.
Accepted:
June 26, 2022.

Published: Resumen
July 20, 2022. Presentación del caso. Paciente fenotípicamente femenina de 18 años de edad, cariotipo 46  XY, que fue evaluada en
Author contribution: centro de atención de tercer nivel de medicina pediátrica, por un cuadro de amenorrea primaria. En la evaluación física se
RACC1 and LECS2: study encontró un adecuado desarrollo mamario, genitales externos femeninos con leve hipotrofia de labios mayores y menores,
conception, RACC1: manuscript canal vaginal de 11 cm; ultrasonido reporta útero rudimentario lineal e imágenes sugestivas a ovarios. La resonancia
design, literature search, data magnética describe presencia de estructura de aspecto tubular bilobulada compuesta por dos imágenes nodulares, las
collection, data or software cuales se ubican adyacentes a la pared vesical en su aspecto posterior, lateral y superior derecho de 27,4 × 15,4 × 11,0 mm.
management. RACC1, LECS2, El conducto inguinal izquierdo presenta en dos imágenes: una nodular sólida, ovoide, isointensa de 37 × 21 × 13,8 mm
LVM3, EJF4: writing, revision and (nodular), quística 22,7 × 14,0 mm, ausencia congénita de útero. Intervención terapéutica. En la exploración laparoscópica
edition. se detectó presencia de gónadas en canal inguinal y paravesical. Se procedió a la resección de ambas gónadas. Evolución
clínica. Se manejó con analgesia, antibiótico y fue dada de alta a los tres días posteriores a la cirugía; la biopsia reportó
Conflicts of interest: criptorquidia de testículo derecho e izquierdo.
The authors declare there are
no conflicts of interest.
Palabras clave
Síndrome de insensibilidad a los andrógenos, feminización testicular, disgenesia gonadal 46  xy, efecto androgénico,
trastornos de diferenciación sexual.

Introduction caused by localized genetic alterations in

the coding sequence of androgen receptors
Androgen insensitivity syndrome (AIS), also linked to the chromosome Xq11  - 
123,
known as testicular feminization syndrome1, which is the gene encoding the androgen
includes a widely varied group of mutations receptor, of a genetically male individual
that is related to androgen receptor (46  XY)3,4. Mild, partial or complete clinical
dysfunction2 and resistance of target tissues entities depend on the degree of androgen
to the action of male hormones3. This is insensitivity3.

[112]
 Advances in genetic causes have allowed care hospital for amenorrhea with normal
these congenital conditions of develop- breast and external genital development.
ment of chromosomal, gonadal or atypical With the surgical history of bilateral inguinal
anatomical sex to be called disorders of hernioplasty at three years of age, in which
sexual differentiation5. they reported as an incidental finding
The main characteristic is the resis- the pre­sence of ovaries in hernial sacs, so
tance of the target tissues to the action they introduced again to the abdominal
of male hormones5,6. The presence of the cavity. He had not initiated sexual activity;
sexual differentiation protein Y promotes telarquia at 12 years, pubic hair appearance
the formation of primordial testicles in the at 13 years, no axillary hair appearance and
fetal abdomen. From the seventh week heterosexual sexual preference. She had no
after conception, the fetal testicles begin other pathological medical history.
to produce testosterone, whose activity Studies were indicated for the suspicion
is blocked by pathological processes that of primary amenorrhea. Laboratory tests
affect androgen receptors7, which prevents reported hormonal alterations related to
the normal male development of the anovulation with a slight elevation of folli-
internal and external genitalia of genetically cle-stimulating hormones and luteinizing
male individuals6,8 and generates the differ- hormones with low testosterone levels
entiation of the external and female geni- (Table 1). Pelvic ultrasonography reported
talia; Wolff duct derivatives which depend that the uterus was sparsely visible, child-
on androgenic action are not developed. sized, with no evidence of endometrium;
The epididymis, deferent ducts and seminal the right ovary of 5 cm3 and the left one of
vesicles9, and the presence of anti-Müllerian 3,9 cm3; no follicles were evident. The karyo-
hormone produced by the primordial testi- type was performed, which reported 46 XY.
cles, suppresses the formation of the female She was evaluated by pediatric urology,
genital organs. However, the lower part of where a diagnostic laparoscopic video was
the vagina is fully developed because it is not indicated. In this procedure, a sample of the
a derivative of the Müller duct. This is shorter apparent right gonad was taken for biopsy.
than normal and has a blind end, lacks The histopathological study reported a
uterus and fallopian tubes7, absent Müllerian tissue consisting of multiple foci of hypo-
or vestigial structures and testicles located plastic seminiferous tubules scattered in
on the lips, inguinal canal or abdomen7. ovarian stroma with granulosa cells, histo-
AIS is one of the common causes of pathological diagnosis ovotestis.
disorders of sexual development that give When she turned 18 years old, she was
rise to varied phenotypes4. A prevalence of referred to the endocrinology outpatient
two to five cases per 100 000 males geneti- clinic from another national hospital, with
cally born has been estimated with an esti- a diagnosis of sexual development disorder
mated incidence of one case per 20 000 to XY, with complete androgen insensitivity
90 000 males genetically born5,10. syndrome suspicion.
The phenotypic spectrum of indivi­duals In the reference hospital, laboratory
depends on the residual activity of the studies were started again, which reported
androgen receptor and ranges from indivi­ maintaining the slight elevation of follicle
duals with a completely female phenotype, stimulating hormones, luteinizing and low
with testicles in the absence of derivatives of testosterone levels (Table 1). Moreover,
the Wolff and Müller ducts and absence of pelvic ultrasonography described the rudi-
sexual hair to a male phenotype with infer- mentary linear uterus 3,7 cm with suggestive
tility and devirilization2,3,12. These variations images of ovaries. It was requested to repeat
define the classification in complete and the revision of the sheets of the previous
partial AIS2. biopsy and a testicular tissue consisting of
The complete AIS was described by underdeveloped seminiferous tubules was
Morris in 1953. This is characterized by reported, some with sclerosis and fibrosis of
presenting in a person of female appearance, the tubular basement membrane arranged
with normal breast development, little body in their fibrous stroma, no spermatogenesis,
hair, primary amenorrhea and undescended no presence of ovarian tissue, diagnosis of
testicles located instead of the ovaries1; it is testicular hypoplasia.
part of the most frequent disorders of sexual Abdomino-pelvic magnetic resonance
differentiation. described the presence of a bilobed tubular
structure, composed of two nodular images,
Case presentation which were located adjacent to the bladder
wall in its posterior, lateral and upper right
This is a phenotypically female patient, aspect of 27,4 × 15,4 × 11,0 mm (Figure 1).
16 years of age, who consulted in a child The left inguinal duct reflected two nodular

DOI: 10.5377/alerta.v5i2.14397
113
Contreras Cruz RA, et al.
 images as a solid, ovoid, isointense of Treatment
37 × 21 × 13,8 mm (nodular) and another
of cystic characteristics of 22,7 × 14,0 mm Surgical intervention was scheduled seven
(Figure 2) and congenital absence of uterus. days after evaluation. The patient was
She was evaluated by the gyneco- admitted to the endocrinology service
logy unit, where she was instructed to three days before her surgery to complete
start hormone replacement therapy, after the pre-surgical evaluations. Prophylaxis
surgical treatment. Also, he referred to the with cefazolin of one gram intravenously
psychological care area where a session was was indicated, 30 minutes before the start
held with the patient’s mother to evaluate of surgery.
her response to diagnosis and treatment. It The surgical procedure consisted of
concluded that gender reinforcement was laparoscopic removal of the gonads by a
not necessary. closed technique. A periumbilical incision
The clinical evaluation of the urology a 10 mm trocar was placed through a peri-
specialty reported that breast development umbilical incision ; the pneumoperitoneum
with Tanner V stage was adecuate. Bila- of 12 mmHg and an initial flow of 5 L/min
teral umbilical and parainguinal scars were were formed. A 5 mm trocar was placed on
evident without other abdominal or inguinal the lower left and right flanks. The presence
canal abnormalities. He also described the of gonads at the level of the bilobed left
female external genitalia with the presence inguinal canal (Figure 3), the bilobed right
of sparse fine pubic hair, distribution of paravesical gonad (Figure 3) and the uterus
genital pubic hair in stage V in the Tanner of linear appearance was evidenced. Finally,
scale, mild hypotrophy of the labia majora the bilateral gonadectomy was performed
and minora, the hymen of annular shape, and sent for histological study.
when performing the vaginal touch, the
wide and functional vaginal canal was iden- Outcome
tified that only allowed the introduction of a
finger, the measurement of the vaginal canal In the immediate postoperative period,
resulted in 11 cm in length. Visualization of the patient was treated with ketorolac
the urethral meatus was difficult. and ceftriaxone intravenously and started

Table 1. Laboratory test results

Laboratory test Pediatric hospital Result of the reference Reference value
results hospital
Follicle stimulating hormone 15,4 mIU/mL 13,19 mIU/mL 2 – 9 mIU/mL
Luteinizing hormone 47,6 mIU/mL 55,51 mIU/mL 1 – 12 mIU/mL
Thyrotropin 0,6 µUI/mL 0,347 µUI/mL 0,3 – 5,6 µUI/mL
Triiodothyronine 2,8 pg/mL 3,64 pg/mL 2,5 – 3,9 pg/mL
Thyroxine 5,2 µg/dL 0,85 ng/dL 0,61 – 1,12 ng/L
Testosterone 1407 ng/mL 12,67 ng/mL 1,75 – 7,81 ng/mL
Estradiol 36,46 pg/mL - 30 – 400 pg/mL
Cortisol AM - 3,45 ug/dL 6 – 23 ug/dL
Prolactin - 16,06 ng/mL 1 –  23 ng/mL

Figure 1. Magnetic resonance image showing right Figure 2. Magnetic resonance image showing left
gonad gonad

Alerta 2022; 5(2):112-117

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Complete androgen insensitivity syndrome
feeding six hours after surgery. Hospital
discharge was indicated on the third post-
operative day. After four days, follow-up was
given for post-surgical evaluation and for
the report of the biopsy that showed vascu-
larized fibromuscular stroma with testicular
tissue. He presented lumenless seminiferous
tubules composed solely of Sertoli cells; the
interstitium presented Leydig cell hyper- a
plasia (Figure 4), without the presence of
epididymis, vas deferens or malignancy. Also,
there are small tubules lined by columnar
epithelium that probably corresponded to
paramesonephric remnants.

Clinical diagnosis
Clinical imaging and histological evaluations
allowed to define the diagnosis of complete b
insensitivity syndrome to androgens or
Morris syndrome.

Discussion
In complete AIS, there is no response to
androgens, which prevents the develop-
ment of any male characteristic and normal
female external genital development
c
occurs12. That is why they are educated
as women and their identity and sexual
inclination are not affected. In addition, its
gonads are azoospermic testicles of variable
localization, they are most often found in
the inguinal ducts, with the presence or not
of epididymis6.
It is unlikely to be diagnosed during
childhood. The detection of an inguinal
hernia or signs of edema in the labia
d
majora in preschool age should make this
syndrome suspect13. The association among Figure 3. a. Endoscopic view of left gonad. b. Endosco-
inguinal hernia in prepubertal girls has been pic view of left gonad and uterus of linear appearance.
known for more than 60 years. Doctors who c. Endoscopic view of right gonad. d. Endoscopic view
of right gonad and uterus of linear appearance
treat inguinal hernias in childhood may
have the first chance to diagnose it6. In these
cases, the diagnosis is made by the patho­
logist after analyzing the surgical piece13. It
is usual to diagnose it during puberty, for
primary amenorrhea, and even later, when
consulting an endocrinologist or gynecolo-
gist for sterility.
Puberty occurs without virilization and
the risk of developing a testicular germ
cell tumor13,14 is 0,02 % in children under
30 years of age; above that age, the risk
increases to 22 %5,7. Therefore, prophylactic
gonadectomy has been recommended
after puberty, when the feminization of
the affected person has completed, since
it is produced in part by testicular estrogen
production and by the peripheral conver-
sion of androgens to estrogens. Only in cases Figure 4. Seminiferous tubules without lumina and
where the testicles are palpated in the groin hyperplastic Leydig cells

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Contreras Cruz RA, et al.
 area and cause discomfort or for aesthetic The differential diagnoses to be taken
reasons, it will be necessary to remove them into account correspond to the deficiency
before puberty, with hormone replacement of the enzyme 5α-reductase, the Mayer-
therapy to initiate puberty until the desired Rokintansky-Küster-Hauser syndrome, the
breast and genital development is reached10. Kallmann syndrome, the pure gonadal
Subsequently, estrogens should be dysgenesis 46 XX, 46 XY, the agenesis of
started at sufficient doses to allow vaginal Leydig cells due to abnormality in the
lubrication and bone gain5,10. For short receptor for luteinizing hormone and the
vaginas, dilation techniques or surgery can enzymatic deficit that are expressed as
be used to allow sexual intercourse and avoid sexual ambiguity at birth18.
dyspareunia. Periodic monitoring should be In the complete AIS, personal character-
maintained in the areas of endocrinology, istics and external genitalia correspond to
gynecology, psychology and urology9,10,15. those of a woman. In general, these women
Morris describes that after castration there do not differ from others with respect to
are hot flashes, vaginal dryness and breast patterns of marriage or other types of rela-
atrophy, so it was not advisable to perform tionships, so it is not often that sex assign-
this procedure1. ment dilemmas arise, although some of
Women who do not accept gonadec- them may present conflicts of sexual iden-
tomy should maintain an annual follow-up, tity19. Hence the importance of multidisci-
due to the risk of malignant degenera- plinary care, and including the collaboration
tion, with pelvic ultrasound and abdomi- of a psychologist or psychiatrist in treatment
no-pelvic magnetic resonance imaging to considerations, to assess the patient’s need
evaluate the size and location of the gonads to reinforce sexual identity; to the family, to
in addition to the verification of tumor prepare them for the sequences of diagnoses
markers such as alpha fetal protein, human and treatments that await them during their
chorionic gonadotropin beta fraction and lifetime9.
lactate dehydrogena16.
It has been described in women with Ethical aspects
normal breast development and high
height, female hair and without baldness, For the publication of this case, the informed
who less frequently present some masculi­ consent of the patient and the person in
nization of external genitalia, such as clito­ charge was obtained, both for the hospital
romegaly or fusion of the lips. In some of the care in which the physical examination was
revisions, it has even been possible to find carried out and for the publication of this
remains of Müller’s ducts (fallopian tubes) in article with the commitment to maintain
up to a third of those affected10. the privacy of the patient, as established in
Testosterone levels rise in the period the Declaration of Helsinki.
of puberty at the same time that follicle
stimulating hormone levels increase with Funding
decreased luteinizing hormone levels, which
suggests that there is androgenic resistance The authors declare that there are no
in the pituitary hypothalamic level17. The sources of funding.
increase in gonadotrophins, as a result of
insensitivity, produces an increase in the Acknowledgments
production of testosterone and estradiol by
Leydig cells5,17. Similarly, because aromatase To endocrinology and pathology staff
activity (an enzyme that transforms services of the Rosales National Hospital for
testosterone into estradiol) is preserved, it their contribution to the care and diagnosis
increases the synthesis of estrogens, which of the case.
are responsible for breast development
during puberty in these individuals5.
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